PROJECT SUMMARY Recent data suggest that ovarian hormones are critical neurobiological risk factors for binge eating in women. Natural increases in these hormones across the menstrual cycle substantially increase risk for binge eating via hormonally induced changes in genetic risk. These data have significantly advanced etiological models and our understanding of the female predominance in eating disorder risk. However, this increased knowledge comes with an urgent public health responsibility. In the US today, 1 in 3 women take hormonal contraceptives that contain combinations of hormones that mimic the hormone levels that are riskiest for binge eating. The relatively commonplace prescription of these contraceptives may substantially increase risk for binge eating in women, particularly in those who are genetically vulnerable to eating disorders. Unfortunately, to date, no study has examined the effects of hormonal contraceptives on risk for binge eating or eating disorders. The long- term goal of the proposed project is to identify, for the first time, the deleterious effects of hormonal contraceptives on binge eating and eating disorder risk and advance public health policy and personalized medicine approaches to women's mental health. Our Specific Aims are to use a multi-method (behavioral genetic, neuroendocrine), longitudinal twin study to examine the between- and within-subject effects of combined oral contraceptives (COCs) on phenotypic and genetic risk for binge eating in women. If COCs increase phenotypic risk for binge eating in women, then there should be significantly higher rates of binge eating in users vs. non-users (a population-level, between-subject effect) and substantial increases in binge eating when COC users are moving from inactive to active pills (an individual-level, within-subject effect). Moreover, if COCs influence binge eating through genetic mechanisms, then there should be significantly increased genetic risk in twins taking COCs (a population-level, between-subject effect) and substantial increases in genetic effects when COC users are moving from inactive to active pills (an individual-level, within-subject effect). We will examine all of these hypotheses in a large sample of female twins (N = 1,532) assessed daily for 45 days using categorical and continuous measures of binge eating. Mixed linear models and twin biometric analyses will be used to investigate phenotypic and genetic effects of COCs on binge eating. The proposed project will be the first to examine the effects of COCs on phenotypic and genetic risk for binge eating and has the potential to significantly advance public health policy and necessitate a re-thinking of basic assumptions about COC prescriptions and use. The clinical implications of our findings run the gamut from requiring physicians to screen for personal and family histories of eating disorders (an uncommon practice) to the selection of alternative contraceptives that are less risky for women. A more personalized approach to COC prescriptions could substantially reduce the prevalence of binge eating and eating disorders.